tbuckley/cabot-search huggingface dataset:
Engineered mesenchymal stem cell-derived extracellular vesicles: A state-of-the-art multifunctional weapon against Alzheimer's disease
Authors: Tong Yin, Yan Liu, Wenbo Ji, Jianhua Zhuang, Xiaohan Chen, Baofeng Gong, Jianjian Chu, Wendanqi Liang, Jie Gao, You Yin
Journal: Theranostics (2023)

With the increase of population aging, the number of Alzheimer's disease (AD) patients is also increasing.According to current estimates, approximately 11% of people over 65 suffer from AD, and that percentage rises to 42% among people over 85.However, no effective treatment capable of decelerating or stopping AD progression is available.Furthermore, AD-targeted drugs composed of synthetic molecules pose concerns regarding biodegradation, clearance, immune response, and neurotoxicity.Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are essential intercellular communication mediators holding great promise as AD therapeutics owing to their biocompatibility, versatility, effortless storage, superior safety, and the ability to transport messenger and noncoding RNAs, proteins, lipids, DNAs, and other bioactive compounds derived from cells.The functionalisation and engineering strategies of MSC-EVs are highlighted (e.g.preconditioning, drug loading, surface modification, and artificial EV fabrication), which could improve AD treatment by multiple therapeutic effects, including clearing abnormal protein accumulation and achieving neuroprotection and immunomodulatory effects.Herein, this review summarises state-of-the-art strategies to engineer MSC-EVs, discusses progress in their use as AD therapeutics, presents the perspectives and challenges associated with the related clinical applications, and concludes that engineered MSC-EVs show immense potential in AD therapy.
Inflammatory extracellular vesicles prompt heart dysfunction via TLR4-dependent NF-κB activation: Erratum
Authors: Vanessa Biemmi, Giuseppina Milano, Alessandra Ciullo, Elisabetta Cervio, Jacopo Burrello, Michele Dei Cas, Rita Paroni, Tiziano Tallone, Tiziano Moccetti, Giovanni Pedrazzini, Sarah Longnus, Giuseppe Vassalli, Lucio Barile
Journal: Theranostics (2023)

[This corrects the article DOI: 10.7150/thno.39072.].
Engineered liposomes to deliver nucleic acid mimics in Escherichia coli
Authors: Luís Moreira, Nuno M. Guimarães, Sara Pereira, Rita S. Santos, Joana A. Loureiro, Rui M. Ferreira, Céu Figueiredo, Maria C. Pereira, Nuno F. Azevedo
Journal: Journal of Controlled Release (2023)

Antisense oligonucleotides (ASOs) composed of nucleic acid mimics (NAMs) monomers are considered as potential novel therapeutic drugs against bacterial infections. However, bacterial envelopes are generally impermeable to naked oligonucleotides. Herein, liposomes loaded with NAMs-modified oligonucleotides (LipoNAMs) were evaluated to deliver ASOs in Escherichia coli. Specifically, we tested several surface modifications that included methoxyPEG conjugated to different lipid anchors or modification of the PEG distal ends with maleimide groups and antibodies. MethoxyPEG coated LipoNAMs showed low delivery efficiency for most bacteria, but maleimide-functionalized PEG LipoNAMs were able to deliver ASOs to nearly half of the bacterial population. Conjugation of antibodies to maleimide-functionalized PEG LipoNAMs increased 1.3-fold the delivery efficiency, enhancing the selectivity towards E. coli and biocompatibility. This work demonstrated for the first time that the coupling of antibodies to PEGylated liposomes can significantly improve the delivery of ASOs in E. coli, which might bring alternative routes for the treatment of bacterial infections in the future.
Skin drug delivery using lipid vesicles: A starting guideline for their development
Authors: Antonio José Guillot, Miquel Martínez-Navarrete, Teresa M. Garrigues, Ana Melero
Journal: Journal of Controlled Release (2023)

Lipid vesicles can provide a cost-effective enhancement of skin drug absorption when vesicle production process is optimised. It is an important challenge to design the ideal vesicle, since their properties and features are related, as changes in one affect the others. Here, we review the main components, preparation and characterization methods commonly used, and the key properties that lead to highly efficient vesicles for transdermal drug delivery purposes. We stand by size, deformability degree and drug loading, as the most important vesicle features that determine the further transdermal drug absorption. The interest in this technology is increasing, as demonstrated by the exponential growth of publications on the topic. Although long-term preservation and scalability issues have limited the commercialization of lipid vesicle products, freeze-drying and modern escalation methods overcome these difficulties, thus predicting a higher use of these technologies in the market and clinical practice.
The association of Medicaid expansion and pediatric cancer overall survival
Authors: Justin M Barnes, Corey Neff, Xuesong Han, Carol Kruchko, Jill S Barnholtz-Sloan, Quinn T Ostrom, Kimberly J Johnson
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Medicaid eligibility expansion, though not directly applicable to children, has been associated with improved access to care in children with cancer, but associations with overall survival are unknown. Data for children ages 0 to 14 years diagnosed with cancer from 2011 to 2018 were queried from central cancer registries data covering cancer diagnoses from 40 states as part of the Centers for Disease Control and Prevention’s National Program of Cancer Registries. Difference-in-differences analyses were used to compare changes in 2-year survival from 2011-2013 to 2015-2018 in Medicaid expansion relative to nonexpansion states. In adjusted analyses, there was a 1.50 percentage point (95% confidence interval = 0.37 to 2.64) increase in 2-year overall survival after 2014 in expansion relative to nonexpansion states, particularly for those living in the lowest county income quartile (difference-in-differences = 5.12 percentage point, 95% confidence interval = 2.59 to 7.65). Medicaid expansion may improve cancer outcomes for children with cancer.
From the Gene to Behavior
Authors: Seymour Benzer
Journal: JAMA (1971)

The problem of gene structure and coding was exciting while it lasted. The story of the past two eventful decades, including my own contributions, has been well told,<sup>1-3</sup>and need not be repeated here. But molecular genetics, pursued to ever lower levels of organization, inevitably does away with itself: the gap between genetics and biochemistry disappears. More recently, a number of molecular biologists have turned their sights in the opposite direction, ie, up to higher integrative levels, to explore the relatively distant horizons of development, the nervous system, and behavior. When the individual develops from an egg, the one-dimensional information contained in the linear sequence of genes on the chromosomes is somehow translated into a two-dimensional blastula, which later folds to produce a precise three-dimensional array of sense organs, central nervous system, and muscles. Finally, the ensemble interacts to produce behavior, a phenomenon which requires four dimensions, at the
Apical Proteins Stimulate Complement Synthesis by Cultured Human Proximal Tubular Epithelial Cells
Authors: SYDNEY TANG, NEIL S. SHEERIN, WUDING ZHOU, ZARIN BROWN, STEVEN H. SACKS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. There is increasing evidence to suggest that the renal tubular epithelium is important in the pathogenesis of progressive renal failure resulting from persistent proteinuria. The role of complement in the progression of chronic renal failure is not well defined. The purpose of this study was to characterize the production of complement by human proximal tubular epithelial cells exposed to serum proteins at the apical surface. Complement C3 gene expression was analyzed by reverse transcription and PCR. C3 protein biosynthesis was confirmed by metabolic labeling followed by immunoprecipitation and quantified by enzyme-linked immunosorbent assay. In the quiescent state, proximal tubular epithelial cells grown on permeable membrane supports secreted C3 predominantly into the apical medium. The addition of 5 mg/ml serum proteins led to an 8.9-fold increase in basolateral C3 secretion and a 2.1-fold increase in apical C3 secretion, altering the ratio of basolateral: apical C3 secretion from 0.44 ± 0.16 to 1.87 ± 0.52. C3 mRNA expression was also upregulated in a time- and dose-dependent manner. Serum fractionation demonstrated that the stimulant responsible for these effects was in the molecular weight range 30 to 100 kD. The observed phenomenon was not reproduced when purified human albumin alone was used as the stimulant. These findings could provide a possible mechanism for the link between proteinuria and interstitial fibrosis. This may have potential implications for strategies directed against complement in retarding the progression of chronic renal failure.
Approaches to Prevention of Firearm Violence
Authors: Robert O. Nathan
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Introducing the Library of Guidance for Health Scientists (LIGHTS)
Authors: Julian Hirt, Christof Manuel Schönenberger, Hannah Ewald, Daeria O. Lawson, Davide Papola, Ramon Rohner, Katja Suter, Shanshan Lin, Federico Germini, Linan Zeng, Ali Shahabinezhad, Saifur Rahman Chowdhury, Ya Gao, Arunima Bhattacharjee, João Pedro Lima, Ana Marusic, Ivan Buljan, Arnav Agarwal, Gordon H. Guyatt, Matthias Briel, Stefan Schandelmaier
Journal: JAMA Network Open (2023)

Importance Improving methodological quality is a priority in the health research community. Finding appropriate methods guidance can be challenging due to heterogeneous terminology, poor indexing in medical databases, and variation in formats. The Library of Guidance for Health Scientists (LIGHTS) is a new searchable database for methods guidance articles. Observations Journal articles that aim to provide guidance for performing (including planning, design, conduct, analysis, and interpretation), reporting, and assessing the quality of health-related research involving humans or human populations (ie, excluding basic and animal research) are eligible for LIGHTS. A team of health researchers, information specialists, and methodologists continuously identifies and manually indexes eligible guidance documents. The search strategy includes focused searches of specific journals, specialized databases, and suggestions from researchers. A current limitation is that a keyword-based search of MEDLINE (and other general databases) and manual screening of records were not feasible because of the large number of hits (n = 915 523). As of September 20, 2022, LIGHTS included 1246 articles (336 reporting guidelines, 80 quality assessment tools, and 830 other methods guidance articles). The LIGHTS website provides a user-oriented search interface including filters for study type, specific methodological topic, research context, guidance type, and development process of the guidance. Automated matching of alternative methodological expressions (eg, enter loss to follow-up and find articles indexed with missing data ) enhances search queries. Conclusions and Relevance LIGHTS is a peer-supported initiative that is intended to increase access to and use of methods guidance relevant to health researchers, statisticians, methods consultants, methods developers, ethics boards, peer reviewers, journal editors, and funding bodies.
RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass
Authors: Nicolas Bonnet, Lucie Bourgoin, Emmanuel Biver, Eleni Douni, Serge Ferrari
Journal: Journal of Clinical Investigation (2023)

The authors recently became aware that an incorrect image was shown in Figure 6F for the Pparb -/-Opg-Fc sample.The correct figure is shown below.The authors regret the error.Figure 6.Bone, muscle, and glucose phenotype of Pparb -/-mice treated by OPG-Fc.(A and B) Skeletal muscle volume of the limb and fat infiltration in muscle evaluated by in vivo microCT.(C) Maximal speed evaluated on treadmill normalized by gastrocnemius mass.(D) Limb force evaluated by handgrip normalized by gastrocnemius mass (n = 8 per group).(E) Body temperature evaluated by infrared camera (n = 8 per group).(F) Muscle fiber type, number, and area.Note the type I fibers in blue dark and type II fibers in light blue.Original magnification is ×10.(G) ITT AUC (n = 8 per group).(H) GTT.(I) Relative protein expression in the gastrocnemius.Hatch marks correspond to mice that have received an acute injection of insulin.(J) Relative mRNA expression of insulin signaling in soleus.(K) Relative mRNA expression of Nfkb signaling in soleus (n = 6 per group).Statistical differences were assessed by 1-way ANOVA.† P < 0.05, ‡ P < 0.01 significant difference versus WT.Bars show mean ± SEM.
Evaluation of the Incidence of Human Papillomavirus–Associated Squamous Cell Carcinoma of the Sinonasal Tract Among US Adults
Authors: Nyall R. London, Melina J. Windon, Ameen Amanian, Fernando T. Zamuner, Justin Bishop, Carole Fakhry, Lisa M. Rooper
Journal: JAMA Network Open (2023)

This case series assesses the incidence of human papillomavirus (HPV)-associated sinonasal squamous cell carcinoma (SNSCC) and the prevalence of HPV-positive SNSCC among US adults.
Tinnitus
Authors: Gregory Luce
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Butyrate ameliorates quinolinic acid–induced cognitive decline in obesity models
Authors: Xing Ge, Mingxuan Zheng, Minmin Hu, Xiaoli Fang, Deqin Geng, Sha Liu, Li Wang, Jun Zhang, Li Guan, Peng Zheng, Yuanyi Xie, Wei Pan, Menglu Zhou, Limian Zhou, Renxian Tang, Kuiyang Zheng, Yinghua Yu, Xu-Feng Huang
Journal: Journal of Clinical Investigation (2023)

Obesity is a risk factor for neurodegenerative disease associated with cognitive dysfunction, including Alzheimer's disease. Low-grade inflammation is common in obesity, but the mechanism between inflammation and cognitive impairment in obesity is unclear. Accumulative evidence shows that quinolinic acid (QA), a neuroinflammatory neurotoxin, is involved in the pathogenesis of neurodegenerative processes. We investigated the role of QA in obesity-induced cognitive impairment and the beneficial effect of butyrate in counteracting impairments of cognition, neural morphology, and signaling. We show that in human obesity, there was a negative relationship between serum QA levels and cognitive function and decreased cortical gray matter. Diet-induced obese mice had increased QA levels in the cortex associated with cognitive impairment. At single-cell resolution, we confirmed that QA impaired neurons, altered the dendritic spine's intracellular signal, and reduced brain-derived neurotrophic factor (BDNF) levels. Using Caenorhabditis elegans models, QA induced dopaminergic and glutamatergic neuron lesions. Importantly, the gut microbiota metabolite butyrate was able to counteract those alterations, including cognitive impairment, neuronal spine loss, and BDNF reduction in both in vivo and in vitro studies. Finally, we show that butyrate prevented QA-induced BDNF reductions by epigenetic enhancement of H3K18ac at BDNF promoters. These findings suggest that increased QA is associated with cognitive decline in obesity and that butyrate alleviates neurodegeneration.
Erector spinae plane block ameliorates acute gastrointestinal injury
Authors: Jing Cai, Yangyang Wang, Ziqing Guo, Hongwei Zhou, Hua Wang, Bo Huang, Guoliang Long, Junjie Chen, Maoyou Shichen, Zheng Ba, Hao Jv, Xuan Liu, Xingxing Liu, Ying Tang, Shiyu Zhou, Zhuang Li, Yuzhan Kang
Journal: Intensive Care Medicine (2023)
Error in Box
Authors: Elinore Kaufman, M Delgado
Journal: JAMA (2023)

would be needed to delineate the costs, options, and benefits of this data collection effort.We firmly agree with Drs Cook and Sills that the secondary psychological and health impacts of witnessing or being near firearm violence are important and are likely far greater than what is currently quantified.For example, in one study, 87% of 10-to 16-year-olds in Philadelphia reported witnessing violence in their communities, 2 with downstream consequences including poor school performance, posttraumatic stress disorder syndrome, future firearm victimization, and handgun carriage. 3-6We concur that national health surveys such as the BRFSS should include exposure to community violence in their data collection and should also make explicit efforts to include the populations at highest risk of such exposure, such as young people living in marginalized and disenfranchised neighborhoods.In keeping with the tenets of trauma-informed care, clinicians should maintain awareness of the potential effects of exposure to violence and should collect these data in routine clinical care.
Reducing HSV-2 Morbidity and Mortality
Authors: Mark D. Pearlman
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Single cell transcriptome and surface protein expression analysis identify <scp>OX40</scp> <sup>+</sup> <scp>GITR</scp> <sup>+</sup> pathogenic T helper 17 in ankylosing spondylitis
Authors: Kijong Yi, Sungsin Jo, Woogil Song, Hae‐In Lee, Hui‐Ju Kim, Ji‐Hyoun Kang, Seon Uk Kim, Seung Hoon Lee, Jinsung Park, Tae‐Hwan Kim, Jeong Seok Lee, Eun Young Lee, Tae‐Jong Kim
Journal: Arthritis & Rheumatology (2023)

To demonstrate the immune landscape of blood and synovial cells in the setting of ankylosing spondylitis (AS) through the analysis of both single-cell transcriptome and surface protein expression, and to unveil the molecular characteristics of pathogenic Th17 cells.This study included 40 individuals with active AS, 20 individuals with stable AS, 40 patients with active rheumatoid arthritis, and 20 healthy controls. Surface phenotype and intracellular staining were assessed using flow cytometry after peripheral blood mononuclear cells and synovial fluid mononuclear cells were stimulated with T cell receptor. Single-cell transcriptomes of 6 patients with active AS were studied along with cellular indexing of transcriptomes and epitopes by sequencing. We also assessed the outcome of targeting OX40 and glucocorticoid-induced tumor necrosis factor receptor (GITR) on the surface of Th17 cells in a mouse model of curdlan-injected SKG mice in which anti-GITR ligand and/or anti-OX40 ligand were used.We identified pathogenic Th17 cells as polyfunctional interleukin-17A (IL-17A)- and interferon-γ (IFNγ)-producing memory CD4+ T cells, with clinically supportive evidence for their pathogenic roles at sites of inflammation in AS. Transcriptome and flow cytometric analyses revealed that the coexpression of TNFRSF4 (OX40) and TNFRSF18 (GITR) is increased in pathogenic Th17 cells. Suppression of ligand receptor interactions in vivo through OX40 and GITR effectively suppressed clinical arthritis and decreased pathogenic Th17 cells in the curdlan-injected SKG mouse model.Our results have implications for the understanding of pathogenic Th17 cells in AS patients and suggest potential therapeutic targets.
Serologic Screening for Genital Herpes
Authors: Gary N. Asher, Cynthia Feltner, Wade N. Harrison, Emmanuel Schwimmer, Caroline Rains, Daniel E. Jonas
Journal: JAMA (2023)

This systematic review to support the 2023 US Preventive Services Task Force Recommendation Statement on serologic screening for genital herpes summarizes published evidence on the benefits and harms of screening and interventions for genital herpes in asymptomatic sexually active adolescents, adults, and pregnant persons with no clinical history of genital herpes.